: Insulin has been shown to regulate many cellular processes including the control of blood glucose levels. It is also capable of regulating over more than 50 proteins, for many of which this level of control has been identified as being at the rate of gene transcription. Insulin's involvement in these processes has been known for years, unfortunately many of the mechanisms for its action are not yet defined. In recent years, enthusiasm has surfaced for using insulin-mimetic agents to help to define these mechanisms as well as to investigate the action of and possible implications of these agents into the design of future treatments of diabetics. In a number of laboratories, oral administration of the insulin-mimetic agent, vanadate, to streptozotocin-induced diabetic rats has been shown to be effective in markedly reducing blood glucose concentrations. In non-diabetic animals oral vanadate appears to have little or no effect on plasma glucose levels. Only within the last year have some reports surfaced where investigators have examined the effects of vanadate on other processes which are also regulated by insulin. These reports include the examination of the effect of vanadate on the expression of transfected PEPCK chimeras in rat hepatoma cells, the induction of the glucose transporter mRNA in NIH 3T3 fibroblasts, the induction of L-type pyruvate kinase mRNA in rat hepatocytes and the increase in pancreatic amylase mRNA in the streptozotocin-induced diabetic rat. To date, however, the investigator is unaware of any reports on the effects of vanadate on an endogenous gene at the level of transcription or of the effect of vanadate on the expression of any gene involved in lipogenesis, a major metabolic pathway highly regulated by insulin. Therefore, the objective of this proposal is to investigate the effect of vanadate on the expression of 2 insulin regulated lipogenic genes, glucose-6-phosphate dehydrogenase and fatty acid synthase. These studies will be carried out using a chemically controlled defined system, the hepatocytes, and a physiologically relevant model, the diabetic animal thus allowing the proper circumstances to critically evaluate the effectiveness of the insulin-mimetic action of vanadate on the regulation of gene expression.